Center for Translational Cancer Nanomedicine

拟议的中心旨在通过开发适当的技术并扩大规模，为在GMP/GLP条件下进行临床前和临床评估的候选药物的测试批次的生产提供快速转换，将我们对广泛的癌症纳米药物进行深入的物理化学、体内处置和成像研究的工作台研究转化为真正的工业产品。我们将在波士顿东北大学(NU)建立一个癌症纳米技术卓越中心(CCNE)，与贝丝以色列女执事医院、哈佛医学院、罗格斯大学、新泽西州立大学、奥本大学和Nemucore医疗创新公司合作。拟议的CCNE将与NIH指定的新泽西癌症研究所和孢子合作。CCNE将利用位于北卡罗来纳州的高速纳米制造中心(NSF资助的纳米科学和工程中心)的支持和设施。 跨学科合作将使基础生物学知识库与物理科学和工程方法相结合，密切参与扩大和制造，迅速将实验室研究转化为动物试验和GMP生产，并缩小抗癌治疗药物发现和开发之间的差距。CCNE将专注于多功能、靶向设备，这些设备将绕过目前的生物障碍，在适当的时间以高局部浓度直接将多种治疗剂输送到癌细胞。该中心的主要目标将是开发、在体外和体内进行临床前测试、表征、扩大规模并在GMP条件下生产最有希望的癌症纳米修复材料的测试批次。纳米载体将包括聚合物胶束、脂质体、聚合物颗粒和树枝状大分子，而将使用的药物将包括促凋亡剂、DNA和siRNA以及诊断标签。拟议的CCNE将：a)创造和提供适当的“起始材料”；b)通过体外研究建立概念验证；c)用动物模型进行药理学研究；d)进行各种体内模型研究；e)提供质量保证；以及f)为癌症治疗和诊断制定一系列广泛的纳米修复材料的生产计划。 公共卫生相关性：我们预计这个示范项目将避免许多独立调查与零碎的基础研究和发展努力相关的问题。该中心是为了在GMP/GLP条件下快速扩大和开发在实验室中显示为有效的抗肿瘤药物而成立的。该中心将提供迅速、有意义的临床试验所需的候选药物的质量和数量。

The proposed Center is designed to provide rapid translation of our bench studies of a broad set of nanomedicines for cancer with in-depth physico-chemical, in vivo disposition and imaging studies into a real industrial product by developing the appropriate technologies and scaling them up for manufacture of test batches of candidates for preclinical and clinical evaluation under GMP/GLP conditions. We will establish a Center for Cancer Nanotechnology Excellence (CCNE) at Northeastern University (NU), Boston with collaborations at Beth Israel Deaconess Hospital; Harvard Medical School; Rutgers, The State University of New Jersey, Auburn University, and Nemucore Medical Innovations, Inc. The proposed CCNE will collaborate with the NIH-designated Cancer Institute of New Jersey and SPORE. The CCNE will utilize the support and facilities of the NU-based Center for High-rate Nanomanufacturing (NSF-funded Nanoscale Science and Engineering Center). Cross-disciplinary collaboration will enable integration of the fundamental biological knowledge base with physical science and engineering approaches for intimate involvement in scale-up and manufacture to rapidly translate bench research into animal testing and GMP production and to narrow the gap between discovery and development of anticancer therapeutics. The CCNE will concentrate on multifunctional, targeted devices that will bypass current biological barriers to delivery of multiple therapeutic agents at high local concentrations, with appropriate timing, directly to cancer cells. The main objective of the Center will be to develop, test pre-clinically in vitro and in vivo, characterize, scale up and manufacture under GMP conditions test batches of the most promising nanopreparations for cancer. Nanocarriers will include polymeric micelles, liposomes, polymeric particles, and dendrimers, while the drugs to be used will include pro-apoptotic agents, DNA, and siRNA together with diagnostic labels. The proposed CCNE will: a) create and supply appropriate "starting materials"; b) establish proof-of-concept through in vitro studies; c) conduct pharmacologic studies with animal models; d) perform a variety of in vivo model studies; e) provide quality assurance; and f) develop production schemes for a broad set of nanopreparations for cancer treatment and diagnosis. Public Health Relevance: We expect this model program will avoid the problems associated with piece-meal basic research, development efforts by many independent investigations. The Center is organized for the rapid scale-up and development, under GMP/GLP conditions, of the drugs shown in the lab to be effective anti-tumor agents. The Center will provide the quality and quantity of drug candidates necessary for prompt, meaningful clinical trials.